Nicolas.Chen_log

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Nicolas.Chen_log

Assignment 2

The article read is written by Chenyu Wei and Andrew Pohorille,
Permeation of Membranes by Ribose and Its Diastereomers, the link to article is listed as following:
DOI: 10.1021/ja902531k


Permeation of Membranes by Ribose and Its Diastereomers By Chenyu Wei and Andrew Pohorille

Introduction
  1. The process of transporting molcecules across biomembrane is important because by studying such mechanism gives the insight of understanding the orgin of life according to the author.
  2. The author pointed out that the ribose is different from other sugar that it is very easy for transportting ribose through the membrane comparing to others.
  3. The signtific problem this paper try to solve is the answer to why ribose has a better permeation because by far it is not clear.
  4. The author used Molecular Dynamics (MD) simulations to solve such problem by actually transport ribose across a POPC membrane.

Methods
  1. MD simulations were calculated using NAMD program.
  2. CHARMM force fild is used and TIP3 water model is employed by the group.
  3. Water-POPC system is setup in a simulation box of 30x30x62 box and equibrumed before productive run.
  4. With a timestep of 1 fs, NPT esemble and then switch to NVT esemble when go into produtive run, simulation is carried out for 5ns.
  5. Free energy calculation using Adaptive Biasing Force method is performed under two different enviroment: a water-hexadecane interface and a water-popc interface.
  6. For the water-headecamne interface run, a 24 angstrom window is used and 7-10ns per window simulation were carried out, for water-POPC window, a 25 angstrom windown is used and in addition to 8-9 ns window, another 17-25 ns simulation were used to snsure the statstical accuracy.
  7. The author compared the populations of different forms of ribose, arabinosem and xylose by their comformations in water and found ribose would favor conformation with equatorial position having the hydroxyl group so for they keep use this conformation.

Results and Discussion
  1. Partition Coefficients between water and hexadecane for ribose, arabinose, and xylose are determined using the free energy calculation.
  2. It is found that ribose partitions in hexadecane better. It is about 1.7 Kcal/mol difference for it to stay in hydrophllic rather than in hydrophobic enviroment.
  3. It is also found the chair conformation is favorable for permeation so this conformation is used for further calculation.
  4. The author points out that atomic simulations is preferred for this kind of simulation rather than using reduced representation of atoms because many of the interactions will required atomic detail to see crucial interactions.
  5. The free energy profile could reveal the permeability of POPC membrane. It is showed that inside the lipid membrane core, according to the ABF calculations, it requires about 9.6-16.4 Kcal/mol for the suger to move across the membrane.
  6. The orientation of the sugar also was monitored during the simulation and the author found it is the membrane-water interface the sugar will stay.
  7. The diffusion coefficient was also studied by the author, to the magnitude of 0.00000001 cm/s.
  8. The author comments on the conformation used in the simulation might affect the accuracy for the simulation because it is important that the hydrogen bonding interaction and the solvlent effect will need to be take into account.
  9. The author also comments ont he relevance to the origins of life by this study. The result of the computer simulation supports the RNA world hypothesis, in which that RNA is said to be the first biological polymers and the first information polymers.

Conclusion
  1. MD simulation was carried out to study the transportation of sugar across the membrane.
  2. The author claims that ribose is faster for move throught the membrane compared to other sugar molecule.
  3. Their results suppot the hypothesis of "RNA world"